Papandreou, ChristopherLi, JunLiang, LimingBulló, MònicaZheng, YanRuiz-Canela, MiguelYu, EdwardGuasch Ferré, MartaRazquin, CristinaClish, Clary B.Corella, DoloresEstruch, RamónRos, EmilioFitó Colomer, MontserratArós, FernandoSerra-Majem, LuisRosique-Esteban, NuriaMartínez-González, Miguel Ángel, 1957-Hu, Frank B.Salas-Salvadó, Jordi2020-04-222020-04-222019Papandreou C, Li J, Liang L, Bulló M, Zheng Y, Ruiz-Canela M, et al. Metabolites related to purine catabolism and risk of type 2 diabetes incidence; modifying effects of the TCF7L2-rs7903146 polymorphism. Sci Rep. 2019 Feb 27; 9(1):2892. DOI: 10.1038/s41598-019-39441-62045-2322http://hdl.handle.net/10230/44303Studies examining associations between purine metabolites and type 2 diabetes (T2D) are limited. We prospectively examined associations between plasma levels of purine metabolites with T2D risk and the modifying effects of transcription factor-7-like-2 (TCF7L2) rs7903146 polymorphism on these associations. This is a case-cohort design study within the PREDIMED study, with 251 incident T2D cases and a random sample of 694 participants (641 non-cases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 years). Metabolites were semi-quantitatively profiled with LC-MS/MS. Cox regression analysis revealed that high plasma allantoin levels, including allantoin-to-uric acid ratio and high xanthine-to-hypoxanthine ratio were inversely and positively associated with T2D risk, respectively, independently of classical risk factors. Elevated plasma xanthine and inosine levels were associated with a higher T2D risk in homozygous carriers of the TCF7L2-rs7903146 T-allele. The potential mechanisms linking the aforementioned purine metabolites and T2D risk must be also further investigated.application/pdfengCopyright © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/MetabòlitsDiabetisinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-019-39441-6info:eu-repo/semantics/openAccess